Staphylococcus aureus is a frequent and major etiological agent of bacterial bovine mastitis, leading to high economic losses. This pathogen readily becomes resistant to many antibiotics, resulting in persistent noncurable intramammary infection (IMI) in animals and the development of multidrug-resistant (MDR) strains. The objectives of this study were to evaluate the prevalence of antimicrobial resistance (AMR) of S. aureus strains causing bovine mastitis in Iran according to published data from 2000 to 2021. As there is still a dearth of information on the AMR of S. aureus from Iranian bovine mastitis, the primary focus and subgroup analysis of the present study was performed on Iranian isolates. A systematic review was done according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Based on the initial search, 1006 article were identified. According to inclusion and exclusion criteria and removing duplications, 55 English articles and 13 Persian articles (a total of 68 articles) were finally analyzed. The highest overall prevalence of resistance was reported against penicillin G (p-estimate = 0.568 for all isolates, and p-estimate = 0.838 for Iranian isolates), followed by ampicillin (p-estimate = 0.554, and p-estimate = 0.670 for all isolates and Iranian isolates, respectively) and amoxicillin (p-estimate = 0.391, and p-estimate = 0.695 for all isolates and Iranian isolates, respectively). Besides, the lowest prevalence of resistant isolates was related to trimethoprim-sulfamethoxazole (p-estimate = 0.108 and 0.118 for all isolates and Iranian isolates, respectively) and gentamycin (p-estimate = 0.163 and 0.190, for all isolates and Iranian isolates, respectively). Our analysis showed that the Iranian isolates were more resistant to all antibiotics than those of all isolates. This difference was significant in the case of penicillin G, ampicillin, and erythromycin at 5%. To the best of our knowledge, except for ampicillin, AMR has increased over time for all the studied antibiotics in Iranian isolates. This increased rate was significant for penicillin G, amoxicillin, and tetracycline (p<0.1). No differences in AMR were detected regarding the mastitis types (clinical vs. subclinical mastitis) for almost evaluated antibiotics. In conclusion, the prevalence of AMR S. aureus isolated from IMI was high particularly for bovine mastitis used antibiotics like penicillin G and ampicillin. Additionally, according to the increasing rate of AMR S. aureus in recent years in Iran, control strategies should be reinforced to avoid the spread of this pathogen and drug resistance.